1. Field of the Invention
This invention relates to granules containing physiologically-active substance, a method for preparing the same and the use thereof. More specifically, this invention relates to granules having such characteristics that a physiologically-active substance or substances contained therein are retained stably under neutral condition and dissolved out therefrom under acidic condition, a method for preparing the same and the use thereof as a feed additive composition.
In the present invention, the term "neutral condition" means a condition having a pH of 5-8 which is equivalent to a condition in the rumen of a ruminant and a condition in the buccal cavity and oesophagus of a mono-gastric animal.
2. Description of the Prior Art
Granules having such properties that a physiologically-active substance or substances contained therein are retained stably under neutral condition but dissolved out under acidic condition are highly useful for living bodies. For example, their usefulness, especially for ruminants, has lately attracted considerable attention.
A ruminant allows a variety of microorganisms to live in its rumen under neutral condition and makes use of their activities to digest and use ingredients such as cellulose, which cannot inherently be digested by a mono-gastric animal. Through physiological and/or nutriological researches on ruminants, the existence of rumens have been pointed out as one of causes for the limited productivity of ruminants in recent years. As a result, a great deal of work is now under way with a view toward allowing a physiologically-active substance, the consumption of which in the rumen is not desired, to pass through the rumen substantially unaltered and to undergo disintegration and absorption in the abomasum and its subsequent digestive tract so that the physiologically-active substance can be used more efficiently. Thus, there has been long-awaited a technique for preparing granules which allow a physiologically-active substance to be retained stably under neutral condition (in rumen) and to dissolve under acidic condition (in abomasum) from the viewpoint of the efficient breeding of ruminants. Such a technique is also useful for physiologically-active substances which are expected to dissolve in the stomach of a mono-gastric animal.
There have already been proposed several methods in relation to the technique which permits substantially unaltered passage of physiologically-active substances through the rumen of ruminants. However, none of the methods appear to be fully effective. For example, German Pat. No. 2212568 discloses granules composed of a biologically-effective substance coated with a film comprising an aliphatic monocarboxylic acid having 14-22 carbon atoms, ricinoleic acid or a mixture thereof, or with a film comprising a salt of each of said acids or a mixture thereof. Japanese Patent Publication No. 45224/1974 discloses a method for preparing an capsule of a fat containing an amino acid which method comprises dispersing an amino acid or polypeptide into a melt mixture consisting of a fat having a melting point of 40.degree. C. or higher and a fat having a melting point lower than 40.degree. C. and pouring the resulting dispersed mixture into water kept at a temperature between 20.degree. C. and 40.degree. C.
Japanese patent publication No. 1057/1981 discloses a biologically-active substance coated with a matrix formed of a saturated, straight-chain or branched, substituted or unsubstituted, aliphatic monocarboxylic acid having at least 14 carbon atoms or salt thereof or a mixture of said saturated acid or its salt and an unsaturated, straight-chain or branched, substituted or unsubstituted, aliphatic monocarboxylic acid having at least 14 carbon atoms or a salt thereof.
Japanese Patent Laid-open No. 154956/1981 discloses a biologically-effective granular substance equipped with a coating film containing an aliphatic monocarboxylic acid having 14-22 carbon atoms or a mixture of salts of some of aliphatic monocarboxylic acids having 14-22 carbon atoms. Reference may also be made to Japanese Patent Laid-open No. 175449/1983, which discloses a biologically-active substance enclosed by a coating film of a protective material which contains one or more substances selected from the group consisting of straight-chain or branched, saturated or unsaturated monocarboxylic acids, hydrogenated vegetable fats and hydrogenated animal fats, and chitosan.
The techniques of German Pat. No. 2212568, Japanese patent publication No. 45224/1974 and Japanese patent publication No. 1057/1981 are accompanied by such drawbacks that the time available for the digestion and absorption is too short to achieve sufficient digestion and absorption, because it is primarily intended to effect the degradation of the coating material in the small intestine and its subsequent digestive tract. In Japanese Patent Laid-open Nos. 154956/1981 and 175449/1983, there are used, with a view toward overcoming the above-mentioned drawbacks, such coating materials that disintegrate to allow one or more substances, effective for the living body, to dissolve out in the abomasum. However, the effectiveness of the techniques cannot be considered to be stable since the degradation of the coating materials in the abomasum does not proceed sufficiently.
Thus, in the existing state of art, there are no satisfactory granules which allow the physiologically-active substance contained therein to be retained stably in the rumen (under neutral condition) and to leach out therefrom in the abomasum (under acidic condition). Therefore, it is the real state of affairs that there is still no satisfactory feed additive compositions capable of passing through the rumen substantially unaltered and dissolving out in the abomasum and its subsequent digestive tract.